Evidence for primary and secondary prevention of coronary artery disease in women taking oestrogen replacement therapy

The increasing use of oestrogen replacement therapy in women has focussed attention on the cardioprotective properties it has demonstrated. Historically, it has been shown that women enjoy a certain protection from heart disease, a phenomenon, however, which has not been studied extensively. Women at every age have less coronary artery disease (CAD) than men, even when various risk factors are accounted for, although the presence of diabetes carries equal mortality for both sexes. However, women who do develop CAD have a greater risk of mortality than men with CAD. Other gender differences include a later age of onset of CAD for women, and a difference in the type of atherosclerotic lesions developed. Most striking is the fact that, in women, high-density lipoprotein (HDL) seems to be a more potent predictor of major cardiovascular events than low-density lipoprotein (LDL), or total cholesterol. The Postmenopausal Oestrogen and Progesterone Interventions (PEPI) Trial looked at changes in HDL, fibrinogen, blood pressure and serum insulin resulting from oestrogen use. Four regimens were compared against placebo in 875 women. The results showed that HDL was increased significantly, LDL decreased significantly, fibrinogen levels decreased significantly, and blood pressure and serum insulin levels were essentially unaffected by oestrogen and oestrogen/progestin interactions. The Heart and Oestrogen/Progestin Replacement (HERS) Study, currently underway, is a secondary prevention trial testing the protective effect of hormone therapy in women with documented CAD. This trial may definitively answer the question of whether hormones protect against CAD. After HERS, it may be unethical to continue conducting placebo-controlled trials in a therapy that has such documented cardioprotective benefit.